Voa generation system and method using a fiber specific analysis

ABSTRACT

A system and method for generating an estimated volume of activation (VOA) corresponding to settings applied to a stimulation leadwire includes a processor performing the following: determining, for each of a plurality of neural elements, one or more respective parameters characterizing an electrical distribution along the neural element, looking up the one or more parameters for each of the neural elements in a look-up table (LUT), obtaining threshold values for each of the neural elements recorded in the LUT in association with the looked-up parameters, comparing, for each of the neural elements, a value of the leadwire settings to each of the respective threshold value, estimating based on the comparisons which of the neural elements would be activated by the settings, and generating a structure corresponding to a region including the neural elements estimated to be activated.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 14/557,640 (“the '640 application”), filed Dec. 2, 2014, whichis a continuation-in-part of U.S. patent application Ser. No. 13/507,962(“the '962 application”), filed Aug. 9, 2012, which claims priority toU.S. Provisional Patent Application Serial Nos. 61/521,583 (“the '583application”), filed Aug. 9, 2011 and 61/690,270 (“the '270application”), filed Jun. 22, 2012. U.S. patent application Ser. No.14/557,640 is also a continuation-in-part of U.S. patent applicationSer. No. 12/454,340 (“the '340 application”), filed May 15, 2009, whichclaims priority to U.S. Provisional Patent Application Serial Nos.61/201,037 (“the '037 application”), filed Dec. 4, 2008, 61/113,927(“the '927 application”), filed Nov. 12, 2008, 61/111,523 (“the '523application”), filed Nov. 5, 2008, 61/079,362 (“the '362 application”),filed Jul. 9, 2008, 61/055,398 (“the '398 application”), filed May 22,2008 and 61/053,449 (“the '449 application”), filed May 15, 2008. Thecontents of all of the '640, '962, '583, '270, '340, '037, '927, '523,'362, '398, and '449 applications are incorporated by reference hereinin their entireties.

FIELD OF THE INVENTION

The present invention relates to a system and method for determining, ona fiber by fiber basis, a volume of activation (VOA) estimated to resultfrom an anatomical stimulation by a stimulation leadwire having appliedthereto clinician-specified stimulation parameter settings.

BACKGROUND

Stimulation of anatomical regions of a patient is a clinical techniquefor the treatment of disorders. Such stimulation can include deep brainstimulation (DBS), spinal cord stimulation (SCS), Occipital NS therapy,Trigemenal NS therapy, peripheral field stimulation therapy, sacral rootstimulation therapy, or other such therapies. For example, DBS mayinclude stimulation of the thalamus or basal ganglia and may be used totreat disorders such as essential tremor, Parkinson's disease (PD), andother physiological disorders. DBS may also be useful for traumaticbrain injury and stroke. Pilot studies have also begun to examine theutility of DBS for treating dystonia, epilepsy, and obsessive-compulsivedisorder.

However, understanding of the therapeutic mechanisms of action remainselusive. The stimulation parameters, electrode geometries, or electrodelocations that are best suited for existing or future uses of DBS alsoare unclear.

For conducting a therapeutic stimulation, a neurosurgeon can select atarget region within the patient anatomy, e.g., within the brain forDBS, an entry point, e.g., on the patient's skull, and a desiredtrajectory between the entry point and the target region. The entrypoint and trajectory are typically carefully selected to avoidintersecting or otherwise damaging certain nearby critical structures orvasculature. A stimulation electrode leadwire used to provide thestimulation to the relevant anatomical region is inserted along thetrajectory from the entry point toward the target region. Thestimulation electrode leadwire typically includes multipleclosely-spaced electrically independent stimulation electrode contacts.

The target anatomical region can include tissue that exhibit highelectrical conductivity. For a given stimulation parameter setting, arespective subset of the fibers are responsively activated. Astimulation parameter may include a current amplitude or voltageamplitude, which may be the same for all of the electrodes of theleadwire, or which may vary between different electrodes of theleadwire. The applied amplitude setting results in a correspondingcurrent in the surrounding fibers, and therefore a corresponding voltagedistribution in the surrounding tissue. The complexity of theinhomogeneous and anisotropic fibers makes it difficult to predict theparticular volume of tissue influenced by the applied stimulation.

A treating physician typically would like to tailor the stimulationparameters (such as which one or more of the stimulating electrodecontacts to use, the stimulation pulse amplitude, e.g., current orvoltage depending on the stimulator being used, the stimulation pulsewidth, and/or the stimulation frequency) for a particular patient toimprove the effectiveness of the therapy. Parameter selections for thestimulation can be achieved via tedious and variable trial-and-error,without visual aids of the electrode location in the tissue medium orcomputational models of the volume of tissue influenced by thestimulation. Such a method of parameter selection is difficult andtime-consuming and, therefore, expensive. Moreover, it may notnecessarily result in the best possible therapy.

Systems have been proposed that provide an interface that facilitatesparameter selections. See, for example, U.S. patent application Ser. No.12/454,330, filed May 15, 2009 (“the '330 application”), U.S. patentapplication Ser. No. 12/454,312, filed May 15, 2009 (“the '312application”), U.S. patent application Ser. No. 12/454,340, filed May15, 2009 (“the '340 application”), U.S. patent application Ser. No.12/454,343, filed May 15, 2009 (“the '343 application”), and U.S. patentapplication Ser. No. 12/454,314, filed May 15, 2009 (“the '314application”), the content of each of which is hereby incorporatedherein by reference in its entirety.

Such systems display a graphical representation of an area within whichit is estimated that there is tissue activation or volume of activation(VOA) that results from input stimulation parameters. The VOA can bedisplayed relative to an image or model of a portion of the patient'sanatomy. Generation of the VOA is based on a model of fibers, e.g.,axons, and a voltage distribution about the leadwire and on detailedprocessing thereof. Performing such processing to provide a VOA previewin real-time response to a clinician's input of parameters is notpractical because of the significant required processing time.Therefore, conventional systems pre-process various stimulationparameter settings to determine which axons are activated by therespective settings.

SUMMARY

According to an example embodiment of the present invention, a methodfor determining an estimated VOA for particular stimulation parametersettings includes analysis of modeled neural elements as a whole,analysis of a voltage field at those neural elements, and determinationof a threshold voltage or activating function at the neural elements atwhich the neural elements are activated for a given parameter setting.However, particularly where a leadwire is used that allows for differentamplitudes to be applied at different ones of the electrodes of theleadwire, the estimated VOA based on the threshold universally appliedto all of the neural elements, may be inaccurate.

Accordingly, in an example embodiment of the present invention, a systemand method includes a processor that analyzes a combination of two ormore shape parameters that characterize electrical attributes of ananatomical region, on a neural element by neural element basis, thatresult from a particular stimulation setting. The shape parametersrelate to an electrical profile along a trajectory of a neural element.For example, as described below, the shape parameters, in an example,characterize the voltage along the neural element or the activatingfunction along the neural element. The neural element can be, forexample, a fiber or a cell with an axon, and is hereinafter referred toas a fiber. The shape parameters may differ between different ones ofthe fibers surrounding the stimulation leadwire. The system isconfigured to determine, for each such combination of shape parameters,a respective threshold stimulation parameter setting at which a fiberhaving the respective combination of shape parameters is activated. Thesystem can store the data, and later reference the data for astimulation setting proposed by a clinician to obtain the thresholds forrespective fibers at that proposed stimulation setting.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

In the drawings, which are not necessarily drawn to scale, like numeralsmay describe similar components in different views. The drawingsillustrate generally, by way of example, but not by way of limitation,various embodiments discussed in the present document.

FIG. 1 is a graph of values for peak voltage and peak activatingfunction (two shape parameters) recorded against respective firingthreshold values, according to which a look-up table can be populated,according to an example embodiment of the present invention.

FIG. 2 includes second difference (i.e., activating function) graphs,showing a correspondence between fiber distance and graph shape.

FIG. 3 is a flowchart that illustrates a method for generating a VOA,according to an example embodiment of the present invention.

FIG. 4 is a diagram that illustrates a system according to an exampleembodiment of the present invention.

FIG. 5 is a graph, prior to interpolation and extrapolation, of valuesfor voltage and activating function with plotted componentsrepresenting, by color and intensity, the required threshold for therespective combined voltage and activating values at which thecomponents are respectively plotted.

FIG. 6 shows a graph after extrapolation and interpolation of theplotted components of FIG. 5.

DETAILED DESCRIPTION

In an example embodiment of the present invention, the system can storeshape parameter and threshold data in a look-up table (LUT). Thereafter,when a clinician inputs a proposed parameter setting of the stimulationleadwire, the system can determine the values of the same combination ofshape parameters for each of the fibers, and then find the stimulationsetting threshold value corresponding in the LUT to the shape parametercombination determined for the fiber. If the input stimulation settingmeets the threshold value obtained from the LUT, the processorgraphically indicates that the respective fiber is activated by the VOAgenerated and displayed based on this fiber by fiber analysis.

In an example embodiment, the processor can initially calculate thethreshold data for each possible combination of shape parameters.Alternatively, the processor can initially calculate first thresholddata for a modeled subset of all possible combinations of shapeparameters, populate the LUT with the first calculated threshold data,and further populate the LUT with threshold data for other combinationsof shape parameters that are not modeled by interpolation and/orsmoothing of the data concerning the modeled shape parameters. Anysuitably appropriate interpolation and/or smoothing method can be used.Additionally or in an alternative embodiment, the processor can furtherpopulate the LUT with threshold data for other combinations of shapeparameters, calculated not by direct modeling, but rather byextrapolation based on the existing directly modeled data concerning themodeled shape parameters. Any suitably appropriate extrapolation methodcan be used.

Alternatively, the processor can initially calculate, and populate theLUT with, the threshold data for a modeled subset of all possiblecombinations of shape parameters. Subsequently, in real time response toclinician input parameters, the system can, for each of a plurality offibers, determine the respective combination of shape parameters, andobtain the threshold stimulation parameter value identified in the LUTfor the respective combination of shape parameters if there is one, and,otherwise, obtain the shape parameter values and respective thresholdvalues of the LUT nearest to those determined for the respective fiberand interpolate, smooth, and/or extrapolate from those values to obtainthe threshold value for the combination of shape parameters for therespective fiber. The obtained shape parameter values can be the nearestsingle combination of shape parameters and its corresponding thresholdvalue or can be a nearest set of shape parameter combinations and theircorresponding thresholds.

In an example embodiment of the present invention, the system initiallyperforms an extrapolation to populate the LUT. Subsequently, inreal-time, the system obtains values from the LUT, which values caninclude the extrapolated values, and performs an interpolation and/orsmoothing on such values (e.g., where an exact match is not alreadyincluded in the LUT), to obtain the relevant information.

In yet another example embodiment, the system performs a two stepextrapolation to populate all data within the convex hull, where in thefirst step, the hull is drawn around an outer boundary of the populateddata, and in the second step, the hull is drawn within the data, so thatthe holes within the interior of the data are considered to be outsidethe convex hull.

For example, FIG. 5 shows modeled threshold values represented by colorand intensity (deep blue representing a low threshold value and deep redrepresenting a high threshold value) plotted against some intersectionsof voltage and activating function values (two example shapeparameters), no threshold values having been modeled for many of theintersections of the represented activating function and voltage values.An overall lip shaped convex hull is formed by the plotted thresholdvalues. In an example embodiment, based on the behavior of the plottedthreshold values within the convex hull, the system extrapolates toapply rules to the intersection of activating function and voltagevalues external to the convex hull and obtain values at those hullexternal intersecting values.

In an example embodiment, the system further interpolates and/orsmoothes the values within the hull to further fill in threshold valuesin the holes within the hull. Such interpolation and/or smoothing canoccur before or after the extrapolation, as mentioned above. In anexample embodiment the interpolation and/or smoothing can be performedafter the extrapolation, the extrapolated values providing further inputdata for a better smoothing in the interpolation and/or smoothing phase.In an example embodiment of the present invention, as mentioned above,the system can be configured to initially populate extrapolated valuesof the LUT, and later perform interpolation in real time where the LUTdoes not include a threshold value for a particular combination of shapeparameters for a given fiber.

In an alternative example embodiment, as noted above, the systemperforms a two-step extrapolation. Referring again to FIG. 5, afterextrapolating values to populate the graph outside the lip-shaped convexhull, new convex hulls can be drawn within the graph, so that the holesof missing data within the lip-shape are located external the newlyconsidered convex hulls. The data surrounding the hulls are thenconsidered, so that, based on the behavior of those surrounding plottedthreshold values, the system extrapolates to apply rules to theintersection of activating function and voltage values external to theconvex hulls, i.e., within the holes, and obtain values at those hullexternal intersecting values, thereby populating the remaining portionsof the graph.

FIG. 6 shows the graph of FIG. 5 modified to be populated withextrapolated and/or interpolated values.

In an alternative example embodiment of the present invention, thesystem can generate an equation or algorithm in the form ofThreshold=f(SP1, SP2) based on the threshold data determined for variousshape parameter combinations, where SP1 is a first shape parameter andSP2 is a second shape parameter. According to an example embodiment inwhich more than two shape parameters are used, the function or methodcan be in the form of Threshold=f(SP1, SP2 . . . SPN). Thereafter, whena clinician inputs a stimulation parameter, the system can determine,for each of a plurality of fibers, the shape parameters for the inputstimulation parameter and obtain the threshold corresponding to theshape parameters using the function. The system can then output a VOAbased on the thresholds determined for those fibers.

In an example embodiment of the present invention, the analyzed shapeparameters can be a combination of a peak voltage across the fiber and apeak of value of an activating function across the fiber. The activatingfunction can be a second difference of the voltage values. For example,for each of the fibers, the system can plot or determine the voltagesand the second difference values of the voltages, and select therespective peak values of each along the respective fiber. See forexample the '330, '312, '340, '343, and '314 applications, which referto a Finite Element Analysis (FEA) program, e.g., Comsol, which can beused to model a voltage field for a given electrode contact combination.The system can then find the input stimulation amplitude parameter atwhich the respective fiber is first activated. For example, the systemcan initially determine the fiber's reaction to a low amplitude, andincrementally increase the amplitude until it is determined that thefiber would be activated by the applied stimulation. For example, asoftware package such as NEURON can be used to determine the stimulationamplitude at which the respective fiber fires. The system can record thedetermined amplitude as the threshold for the respective pair of shapeparameters, i.e., peak voltage and peak of second difference of thevoltages. FIG. 1 shows an example graph of values for peak voltage andpeak activating function (second difference) recorded against respectivefiring threshold values.

Thereafter, during use of the system by a clinician, the system can, ona fiber by fiber basis, (a) determine the voltage distribution andsecond difference values of those voltages (according to otherembodiments, different shape parameters can be determined), (b) selectthe peak of those values along the respective fiber, (c) look up thethreshold amplitude previously recorded by the system for those peakvalues, (d) and set the fiber as being activated if the input amplitudesetting meets the threshold and otherwise as not being activated. Thesystem can then graphically display a VOA including all of the fiberswhose corresponding thresholds are at or below the input amplitudesetting. It is noted that different steps can be performed by differentterminals/processors. For example, a first terminal/processor canexecute software for determining the thresholds. A secondterminal/processor can be operated by a clinician to input the amplitudeparameter and can select the previously recorded thresholds to determinewhether the respective fibers would be activated at the input amplitudeand accordingly output a VOA.

The peak voltage and second difference value can characterize very wellthe shape information concerning the distribution of electrical valuesof the respective fibers because they represent the height and spread ofthe value distribution, which is also dependent on distances of therespective fibers from the electrodes. For example, FIG. 2 shows graphsof the values of the second difference of voltages plotted against nodesof a respective fiber, where the center node is represented by the valueof 0 on the abscissa and where each graph corresponds to a respectivefiber. The second difference values of FIG. 2 have been normalized topeak at 1. (However, normalization can be to other values instead.) Itis noted that, while the graphs can represent stimulation at negativeamplitude, such that the voltages can all be below 0, the seconddifference values can still include values both below and above 0. Thegraph represented by the plain solid line corresponds to a fiber that isfurthest from the leadwire, of the three fibers represented by thegraphs in the figure. The graph represented by the dashed linecorresponds to a fiber that is between those fibers of the three thatare closest and farthest from the leadwire. The graph represented by thedotted solid line corresponds to the fiber of the three that is closestto the leadwire. It can be seen that the closer the fiber is to theleadwire, the less the spread of the graph, which spread ischaracterized by the peak voltages and second difference values.

In other example embodiments, surrogate shape parameters can be used forcharacterizing a fiber. For example, since electrical values at a fibercan be dependent upon distance from electrical source, the distance canbe a surrogate value for a shape parameter. In an example embodiment, aplurality of shape or other parameters can be used to characterize afiber. In an example embodiment, different parameters are differentlyweighted in a function whose output is used as the characterization ofthe fiber. For example, weighted parameters of a fiber can include,voltage, current density, distance, some activating function, etc.

In an example embodiment of the present invention, the shape parameterscharacterizing the respective fibers for which the system initiallydetermines the respective thresholds to be recorded are those prevalentat the fibers at unit amplitude, e.g., unit current or unit voltage, forexample, where the sum of all amplitudes of all of the electrodes of agiven polarity of the leadwire is 1, i.e., they have a combined totalmagnitude of 1. Although all recorded shape parameter combinations aretaken at a combined unit current or voltage, various shape parametercombinations are recorded because of different ratios at which thecombined unit current or voltage are applied to the various electrodesof the leadwire. For example, where a leadwire includes four electrodes,a first shape parameter combination can be recorded for an equaldistribution of 25% of the unit current or voltage at each of theelectrodes, and a second shape parameter combination can be recorded fora distribution of 50%, 25%, 12.5%, and 12.5%. After the shape parametersextant at unit current or voltage are obtained, the system canincrementally increase the applied current or voltage, but at the sameratio of distribution to the electrodes, and can record, for each of thefibers, the, for example, total, current or voltage value at which therespective fiber is activated. Subsequently, when the clinician inputsstimulation parameters, the system can similarly, for each of thefibers, determine the shape parameter combination values at a unit totalamplitude with the same electrode distribution ratio as that of theclinician's input values, look up the recorded threshold stimulationamplitude for the respective shape parameter combination values, anddetermine whether the fiber would be activated by the clinician's inputamplitude by comparing the input amplitude to the recorded thresholdstimulation amplitude.

FIG. 3 is a flowchart that shows steps for determining an estimated VOAfor a clinician's input stimulation parameters, according to an exampleembodiment. At step 300, the system and method obtains shape parametersat until total amplitude for each of a plurality of fibers, for each ofa plurality of settings. At step 302, the system and methodincrementally increases the amplitude for each of the plurality ofsettings, and, for each of the fibers, records the amplitude at whichthe respective fiber is activated. It is noted that step 300 need not beperformed completely for all of the plurality of settings prior toperformance of step 302. Instead, step 302 can be performed for any onesetting immediately following performance of step 300 for thatrespective setting. It is also noted that the plurality of settings forwhich steps 300 and 302 are performed need not include all possiblesettings, as explained above.

At step 304, the system and method obtains clinician parameter input,including an amplitude setting. At step 306, the system and methodnormalizes the clinician amplitude input to a normalization value, e.g.,unit total amplitude.

At step 308, the system and method obtains shape parameters for eachfiber at the normalized clinician amplitude input. At step 310, thesystem and method, for each fiber, looks up the threshold recorded forthe shape parameters corresponding to the respective fiber. At step 312,the system and method, for each of the fibers, compares the obtainedrespective threshold to the clinician input amplitude to determinewhether the fiber is estimated to be activated at the clinician inputamplitude. It is noted that step 308 need not be performed completelyfor all of the plurality of fibers prior to performance of step 310, andthat step 310 not be performed completely for all of the plurality offibers prior to performance of step 312. Instead, step 310 can beperformed for any one fiber immediately following performance of step308 for that respective fiber, and step 312 can be performed for any onefiber immediately following performance of step 310.

At step 314, the system and method generates or updates a VOA based onthe activated fibers.

It is noted that different steps illustrated in FIG. 3 can be performedby different processors and terminals. For example, a set-up system canperform steps 300 and 302, which can be time intensive. The results canbe loaded on a memory device at, and/or for access by, a secondprocessor and terminal at which a clinician may input parameters forwhich the processor can access the previously stored results todetermine and output the VOA.

FIG. 4 shows a system according to an example embodiment of the presentinvention. One or more LUT(s) 410 are stored in a memory 400. Aclinician can input, via an input device 402, parameter settings,including amplitudes for one or more electrodes of a leadwire. Aprocessor 404 can look up, in the LUT(s) 410, threshold values for eachof a plurality of fibers surrounding the leadwire to determine which ofthe respective fibers are estimated to be activated at the clinicianinput parameters. The processor can output a VOA 412 in a graphical userinterface (GUI) presented in a display device 406. The VOA can bedisplayed relative to a model of the leadwire 414.

It is noted that the recorded thresholds can be the amplitude thresholdsdirectly or some surrogate value. For example, thresholds can berecorded in terms of current density or another electrical parameter.

Settings other than amplitude, such as pulse width, may affectactivation. Accordingly, the system can further determine the thresholdof a fiber having certain shape parameters for a particular combinationof one or more of such other settings. For example, different thresholdscan be recorded for a fiber for different pulse widths. In an exampleembodiment, the system can initially run a simulation for each pulsewidth allowed by the software to find the respective thresholds at whichthe respective fibers having respective shape parameter combinationsfirst fire for each such pulse width. Alternatively, the system caninitially determine such thresholds for a subset of the possible pulsewidths, and then extrapolate and/or interpolate the data to obtainthresholds for other pulse widths that have not been simulated. All suchdata can be recorded for later threshold lookup in response to clinicianinput of an amplitude setting at a particular pulse width.Alternatively, as noted above interpolation may be performed inreal-time. In an example embodiment, a single LUT stores the thresholddata for all combinations of shape parameter combinations and pulsewidths. Alternatively, a separate LUT is stored per pulse width, whichcan be more efficiently processed in response to clinician input of anamplitude setting, by implementing a two-step process of initiallyselecting an LUT based on pulse width, and then finding the thresholdsfor the fibers in the selected LUT. According to this latter embodimentand according to the embodiment in which the system does not simulateall possible pulse widths, but rather extrapolates and/or interpolatesdata for difference pulse widths, the system can initially record LUTsfor respective ones of a subset of possible pulse widths, and thenextrapolate and/or interpolate from the data of various ones of the LUTsto obtain new LUTs for non-simulated ones of the possible pulse widths.

Aside from pulse width, the data can be further broken down into othergroups of data. For example, in an example embodiment, the systemfurther separately stores data for cathodic and anodic arrangements. Inthis regard, each fiber can be separately characterized as activated byeither the cathode or anode, and the appropriate data accessed to obtainits respective threshold. For example, where present clinician settingsare such that a particular fiber is affected by the cathode, thresholddata for a cathodic arrangement is accessed, and vice versa.

In an alternative example embodiment, whether cathodic or anodic data isaccessed to obtain the threshold information is determined by thearrangement as a whole, rather than on the fiber by fiber basisdescribed above. According to this example embodiment, where the IPG canis assigned as the sole anode and the cathodes are all on the leadwire,the configuration is treated on a whole as cathodic, and cathodic datais accessed to determine the threshold for all of the fibers. Otherarrangements can be considered anodic arrangements. This describedcharacterization of arrangements as anodic or cathodic is exemplary, andother factors can be used to characterize an arrangement as cathodic oranodic.

While voltage and activating function have been described as an shapeparameter combination, other shape parameters can be used instead or inaddition. Other shape parameters can include, for example, a windowedactivating function, a transmembrane potential V_(m) (see Warman et al.,“Modeling the Effects of Electric Fields on nerve Fibers: Determinationof Excitation Thresholds,” IEEE Transactions on Biomedical Engineering,Vol. 39, No. 12, pp. 1244-1254 (December 1992), the entire content ofwhich is hereby incorporated by reference herein), and a distance oreffective distance function (see Butson et al., “Current Steering toControl the Volume of Tissue Activated During Deep Brain Stimulation,”Brain Stimul. 2008 January; 1(1): 7-15, the entire contents of which ishereby incorporated by reference herein; see also Butson et al., “Roleof Electrode Design on the Volume of Tissue Activated During Deep BrainStimulation,” J. Neural Eng. 2006 March; 3(1): 1-8, published online onDec. 19, 2005, the entire contents of which is hereby incorporated byreference herein). It is further noted that a weighted combination of aplurality of parameters, e.g., parameters described above, can be usedas a shape parameter.

The generation of a VOA, including the necessary modeling and look-upson a fiber by fiber basis, as described above may require moreprocessing time than generation based on an estimation for all fibers asa whole. Therefore, in an example embodiment of the present invention,the system and method provide VOA information in a piecemeal manner toquicken an initial response time to a clinician's input parameters. Todo so, the system can initially determine and display a VOA based onthreshold values for a subset of the fibers, and incrementally sharpenthe VOA by subsequently determining the threshold values for more of thefibers. For example, the first displayed VOA can be based on thresholdvalues of every fourth fiber, a second displayed VOA can be based onthreshold values of every second fiber, etc. In an example embodiment,the described increase to the spatial resolution can be performedselectively at the VOA boundary as determined by the lower resolution,because it may be assumed that all fibers within the boundary determinedby the lower resolution are also activated. For example, a firstdisplayed VOA can be based on threshold values of every fourth fiber, asecond displayed VOA can be based on the first displayed VOA and thethreshold values of every second fiber that is in between two adjacentdiscordant fourth fibers, etc.

In an example embodiment, the system uses another form of piecemealoutput of the VOA, which can be used by the system as an alternative tothe above-described method or additional to it, by which the systemfirst performs a linear estimation to generate the first displayed VOA,and then uses a non-linear model of the fiber to update the display ofthe VOA. For example, after use of the linear method by which to quicklyprovide a display of a VOA, the system uses a very accurate, but slower,non-linear method that uses numerical integration for refining thedisplayed VOA

In an example embodiment of the present invention, a further method forincreasing response time, which can be used instead of or in addition tothe above-described method of initially displaying a coarse VOA, caninclude initially finding an approximate grid size of the VOA and thenfinding all of the threshold values within the grid (for example for allfibers or, as described above, initially for a subset of the fiberswithin the grid and then incrementally for more and more of the fibers).For example, the system can store for each of a plurality of amplitudevalues (e.g., of a combination of all active electrodes of theleadwire), a respective expected grid size. In response to theclinician's amplitude input, the system can determine whether any of thefibers at a perimeter of the grid size stored in association with theclinician's amplitude input is estimated to be fired. If none isestimated to be activated, the system reduces the grid size, until atleast one fiber at the perimeter is estimated to be activated, anddetermines which of the remaining fibers within the grid are estimatedto be activated, for example all of the remaining fibers on a finegranular basis, or initially coarsely and then incrementally morefinely, as described above.

In an example embodiment, as soon as the system determines that any ofthe fibers at the perimeter of the associated grid is estimated to beactivated, the system can obtain a larger grid, and again determinewhether any of the fibers at the perimeter is estimated to be activated.The system can repeat this until a grid is found in which none of thefibers at the perimeter thereof is estimated to be activated, and canthen determine, for each of the fibers within the grid (or a coarsesubset thereof), whether the respective fiber is estimated to beactivated, the combination of all of the fibers estimated to beactivated forming the VOA.

In an example embodiment of the present invention, a Marching Squares orCubes algorithm can be used to generate the VOA. For example, afterobtaining the threshold values of the modeled fibers, the system canapply the Marching Cubes algorithm to determine the locations betweenthe fibers having the necessary threshold for activation at theclinician's input settings. In this regard, although individual fibersare modeled and evaluated, the actual location of fibers in ananatomical region may be unknown. Therefore, all of the spacesurrounding the leadwire is ultimately treated as potential fiberlocations, and the system determines where activation would occur insuch space if fibers were included in the space. For each fiber, thiscan be performed for each adjacent surrounding fiber, e.g., each of fourfibers surrounding the center fiber and offset at 90° from each other.That is, locations between a fiber and each of its four surroundingfibers, which locations meet the threshold, can be determined. A linedrawn between such threshold points surrounding the center fiber canform a boundary.

In a variant of this embodiment, the system and method can first findeach pair of adjacent fibers whose threshold values are respectivelyabove and below the actual input value, and can then apply the MarchingCubes algorithm selectively to only such pairs of adjacent fibers toobtain the VOA. Such a selective application of the Marching Cubesalgorithm may speed response time. Stated otherwise, the system andmethod can initially search for those cubes of a grid whose verticesmeet exactly (as opposed to exceeding or being below) the desiredthreshold, and can selectively apply the Marching Cubes algorithm toonly those cubes.

In an example embodiment of the present invention, where the settings ofthe leadwire electrodes are rotationally symmetric about the leadwire,the system and method can determine a portion of the VOA at one side ofa plane that longitudinally intersects the center of the leadwire alongits length, according to one or more of the methods described above (oraccording to other methods), and can then revolve the result around theleadwire to complete the VOA, instead of performing the calculations,modeling, and/or look-ups for all of the fibers surrounding theleadwire. In this regard, while fibers at different locations maydifferently react to the same electrode parameters, the inventors havediscovered that this is usually so for fibers at different longitudinallocations of the leadwire, but that fibers that are at the samelongitudinal location but rotationally offset with respect to theleadwire usually react similarly to the same electrode parameters.

An example embodiment of the present invention is directed to one ormore processors, which can be implemented using any conventionalprocessing circuit and device or combination thereof, e.g., a CentralProcessing Unit (CPU) of a Personal Computer (PC) or other workstationprocessor, to execute code provided, e.g., on a hardwarecomputer-readable medium including any conventional memory device, toperform any of the methods described herein, alone or in combination.The one or more processors can be embodied in a server or user terminalor combination thereof. The user terminal can be embodied, for example,a desktop, laptop, hand-held device, Personal Digital Assistant (PDA),television set-top Internet appliance, mobile telephone, smart phone,etc., or as a combination of one or more thereof. Specifically, theterminal can be embodied as a clinician programmer terminal, e.g., asreferred to in the '330, '312, '340, '343, and '314 applications.Additionally, as noted above, some of the described methods can beperformed by a processor on one device or terminal and using a firstmemory, while other methods can be performed by a processor on anotherdevice and using, for example, a different memory. In an exampleembodiment, the look up tables can even be stored on an implantablemedical device (IMD) with which the clinician programmer terminalcommunicates via a telemetry device.

The memory device can include any conventional permanent and/ortemporary memory circuits or combination thereof, a non-exhaustive listof which includes Random Access Memory (RAM), Read Only Memory (ROM),Compact Disks (CD), Digital Versatile Disk (DVD), and magnetic tape.

An example embodiment of the present invention is directed to one ormore hardware computer-readable media, e.g., as described above, havingstored thereon instructions executable by a processor to perform themethods described herein.

An example embodiment of the present invention is directed to a method,e.g., of a hardware component or machine, of transmitting instructionsexecutable by a processor to perform the methods described herein.

The above description is intended to be illustrative, and notrestrictive. Those skilled in the art can appreciate from the foregoingdescription that the present invention can be implemented in a varietyof forms, and that the various embodiments can be implemented alone orin combination. Therefore, while the embodiments of the presentinvention have been described in connection with particular examplesthereof, the true scope of the embodiments and/or methods of the presentinvention should not be so limited since other modifications will becomeapparent to the skilled practitioner upon a study of the drawings,specification, and the following listed features. For example, while thedescriptions above specifies certain therapies, the above-describedfeatures can similarly be applied to other forms of electrode therapy.

What is claimed is:
 1. A computer system for generating an estimatedvolume of activation (VOA), the system comprising: a computer processorconfigured to: for each of a plurality of neural elements that are in avicinity of a leadwire: determine a respective threshold activationvalue; and determine whether a user-input stimulation value to beapplied to the leadwire meets the respective threshold activation valueof the respective neural element; and generate a surface structurecorresponding to those of the neural elements whose respective thresholdactivation values have been determined to be met by the user-inputstimulation value; wherein, for each of the plurality of neuralelements, the determination of the respective threshold value includes:determining at least one of a peak voltage level along the respectiveneural element or a peak second difference voltage values along therespective neural element; and obtaining the respective threshold valuebased on the respective determined at least one of the peak voltagelevel or the peak second difference voltage value.
 2. The system ofclaim 1, wherein the determined at least one of the peak voltage levelor the peak second difference voltage value includes both the peakvoltage level along the respective neural element and the peak seconddifference voltage value along the respective neural element.
 3. Thesystem of claim 2, wherein the obtaining of the respective thresholdvalue includes looking up a combination of the determined peak voltagelevel and the determined peak second difference voltage value in alook-up table that pairs a respective threshold value with each of aplurality of combinations of (a) a respective voltage level and (b) arespective second difference value.
 4. The system of claim 1, whereinthe determined at least one of the peak voltage level or the peak seconddifference voltage value includes the peak voltage level along therespective neural element, wherein the obtaining of the respectivethreshold value includes looking up the respective determined peakvoltage level in a look-up table that pairs a respective threshold valuewith a respective voltage level.
 5. The system of claim 1, wherein thedetermined at least one of the peak voltage level or the peak seconddifference voltage value includes the peak second difference voltagevalue along the respective neural element, wherein the obtaining of therespective threshold value includes looking up the respective determinedpeak second difference voltage value in a look-up table that pairs arespective threshold value with a respective second difference voltagevalue.
 6. The system of claim 1, wherein the leadwire is arranged toprovide an anodic stimulation.
 7. The system of claim 1, wherein theuser-input stimulation value includes one of a current amplitude and avoltage amplitude.
 8. The system of claim 1, wherein the user-inputstimulation value includes a respective distinct stimulation value foreach of a plurality of contacts of the leadwire.
 9. The system of claim8, wherein the respective distinct stimulation values include currentvalues.
 10. The system of claim 1, wherein the leadwire is configured toprovide a deep brain stimulation (DBS) therapy.
 11. The system of claim1, wherein the leadwire is configured to provide a spinal cordstimulation (SCS) therapy.
 12. The system of claim 1, wherein theleadwire is configured to provide an Occipital NS therapy.
 13. Thesystem of claim 1, wherein the leadwire is configured to provide aTrigemenal NS therapy.
 14. The system of claim 1, wherein the leadwireis configured to provide a peripheral field stimulation therapy.
 15. Thesystem of claim 1, wherein the leadwire is configured to provide asacral root stimulation therapy.
 16. A computer implemented method forgenerating an estimated volume of activation (VOA), the methodcomprising: for each of a plurality of neural elements that are in avicinity of a leadwire: determining, by a computer processor, arespective threshold activation value; and determining, by the computerprocessor, whether a user-input stimulation value to be applied to theleadwire meets the respective threshold activation value of therespective neural element; and generating, by the computer processor, asurface structure corresponding to those of the neural elements whoserespective threshold activation values have been determined to be met bythe user-input stimulation value; wherein, for each of the plurality ofneural elements, the determination of the respective threshold valueincludes: determining, by the computer processor, at least one of a peakvoltage level along the respective neural element or a peak seconddifference voltage values along the respective neural element; andobtaining, by the computer processor, the respective threshold valuebased on the respective determined at least one of the peak voltagelevel or the peak second difference voltage value.
 17. The method ofclaim 16, wherein the determined at least one of the peak voltage levelor the peak second difference voltage value includes both the peakvoltage level along the respective neural element and the peak seconddifference voltage value along the respective neural element.
 18. Themethod of claim 17, wherein the obtaining of the respective thresholdvalue includes looking up a combination of the determined peak voltagelevel and the determined peak second difference voltage value in alook-up table that pairs a respective threshold value with each of aplurality of combinations of (a) a respective voltage level and (b) arespective second difference value.
 19. The method of claim 16, whereinthe determined at least one of the peak voltage level or the peak seconddifference voltage value includes the peak voltage level along therespective neural element, wherein the obtaining of the respectivethreshold value includes looking up the respective determined peakvoltage level in a look-up table that pairs a respective threshold valuewith a respective voltage level.
 20. The method of claim 16, wherein thedetermined at least one of the peak voltage level or the peak seconddifference voltage value includes the peak second difference voltagevalue along the respective neural element, wherein the obtaining of therespective threshold value includes looking up the respective determinedpeak second difference voltage value in a look-up table that pairs arespective threshold value with a respective second difference voltagevalue.